Chromatin remodeling factor Brg1 in embryonic development

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Abstract/Contents

Abstract
During embryonic development, dynamic remodeling of the chromatin landscape is required for the transcriptional machinery to access the genomic DNA in a spatiotemporally controlled manner. This intricate level of regulation allows precise gene regulation, necessary for complex morphogenetic processes. The Brg1/Brm-associated factor (BAF) complex is a multisubunit, ATP-dependent chromatin remodeling complex. Among the subunits, Brg1 is an ATPase that is critical for the function of the complex. Here, we study the role of Brg1 in foregut and cardiac outflow tract development. In the foregut, Brg1 functions with HDAC proteins in the ventral epithelium to regulate Nkx2-1 expression, essential for foregut septation into trachea and esophagus. In the absence of Brg1, embryos develop a single-tube foregut, reminiscent of human patients with tracheoesophageal fistula. In the developing heart, Brg1 functions in the secondary heart field-derived myocardium to control Semaphorin 3c (Sema3c) expression, essential for the outflow tract to septate into pulmonary artery and aorta. Deletion of Brg1 in the secondary heart field results in decreased neural crest cell colonization of the outflow tract, leading to a phenotype similar to the persistent truncus arteriosus pathology. Brg1 cooperates with HDAC proteins and Chd7 in the outflow tract myocardium to control Sema3c expression. These studies demonstrate novel functions and molecular mechanisms of Brg1 in foregut and cardiovascular development.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2013
Issuance monographic
Language English

Creators/Contributors

Associated with Lin, Chien-Jung
Associated with Stanford University, Cancer Biology Program.
Primary advisor Scott, Matthew P
Thesis advisor Scott, Matthew P
Thesis advisor Axelrod, Jeffrey (Jeffrey David)
Thesis advisor Giaccia, Amato J
Thesis advisor Koong, Albert
Thesis advisor Red-Horse, Kristy
Advisor Axelrod, Jeffrey (Jeffrey David)
Advisor Giaccia, Amato J
Advisor Koong, Albert
Advisor Red-Horse, Kristy

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Chien-Jung Lin.
Note Submitted to the Program in Cancer Biology.
Thesis Thesis (Ph.D.)--Stanford University, 2013.
Location electronic resource

Access conditions

Copyright
© 2013 by Chien-Jung Lin
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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